See instructions): Physical inactivity is a major cause of preventable morbidity and premature death in theU.S. Enhanced physical activity helps build and maintain healthy bones, muscles and joints, prevent joint swelling and soreness from arthritis, helps sustain independent living, and reduces the risk of developing diabetes, obesity, ischemic heart disease, dyslipidemia, and hypertension. Little is known about the mechanisms responsible for these benefits but they appear to be realized through complex interactions among molecules, cells, and systems. Understanding these mechanisms requires an integrative approach because of the encompassing responses caused by physical activity. Driven by these factors, we have designed this training program to prepare independent investigators interested in evaluating how activity/inactivity impacts function/dysfunction at all levels of inquiry. We employ multidisciplinary training experiences that include research in gene regulation, cell physiology, bio- chemistry, systems physiology, whole body responses and patient assessment and intervention. Trainees can use reductionist approaches of molecular and cell physiology to apply to the integrated responses of the whole and relate their implications to health and disease. This is achieved by 24 faculty appointed in Biomedical Sciences, Physiology, Internal Medicine, Nutritional Sciences, Physical Therapy, and the School of Nursing. There is excellent University support for this program with targeted recruitments in the area of activity/inactivity and health. Existing interactions among faculty include collaborations in research, trainee mentoring, and grant awards. All participating faculty maintain active research programs that are supported by over 58 nationally competitive grants contributing to >$10.7 M/yr direct costs of research support. Currently 34 predoctoral and 14 post- doctoral trainees are being mentored by the participating faculty. A majority of predoctoral trainees come to the program to study with specific faculty. Predoctoral trainees will work in four departmental graduate programs with degree requirements that facilitate specialized training related toactivity/ inactivity. Four predoctoral and four postdoctoral trainees are requested for the years of this renewal. Management of the training program is by the Director, Assistant Director and an Advisor Committee comprised of four faculty members representing the breadth of research approaches. The success of this program is marked by the achievements of previous trainees who have excelled in research careers in university settings. RELEVANCE (Seeinstructions): Physical inactivity is a major cause of preventable morbidity and prematuredeath in the U.S. Enhanced physical activity helps build and maintain healthy bones, muscles and joints, preventjoint swelling and soreness from arthritis, helps sustain independent living, and reduces the risk of developingdiabetes, obesity, ischemic heart disease,dyslipidemia, and hypertension. This programwill train young investigators to evaluate how activity/inactivity impacts function/dysfunction and relate this to health and disease.